Since just about everything to do with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is disputed, it’s no surprise that there has been controversy surrounding the PACE trial from the start. But now this argument threatens to become much wider and drag in a large part of academic research, any study, in fact, in any field, that involves human participants.

The publicly funded PACE trial, published in 2011 in The Lancet, compared different interventions (Cognitive Behavioural Therapy, Graded Exercise Therapy, Adaptive Pacing Therapy and Specialist Medical Care) for ME/CFS. Since its inception the study has been criticized by patients, and after its publication they made a series of Freedom of Information requests for the data. The responsible research centre, Queen Mary University of London, has received 35 requests for 160 pieces of information. Many have been rejected, deemed vexatious, on the grounds that patients were waging a campaign to discredit the trial.

This dispute, largely until that point between patients and the investigators, escalated at the end of last year after a series of blog posts by David Tuller and the intervention of Professor James Coyne. Coyne, who has a long history of exposing and debunking pseudoscience, made his own request for the data from the publishers of a PACE follow-up study on the cost effectiveness of the interventions. This study was not in the Lancet but carried by PLOS One, which has a stated policy of data sharing. Coyne applied under the PLOS One regulations in force at the time of publication.

At first, Coyne was also told his request was being rejected as vexatious. This was clearly absurd: Coyne is well respected with an excellent reputation, indeed could be argued as having a bigger career reach than any of the trial investigators. It was then suggested that trial data could not be properly anonymized. This reason was in turn dropped: a sibling trial, FINE, had shared data, and the FOI commissioner recently ruled on another PACE request by patients that the data could be anonymized. Peter White, the most senior of the trial principal investigators (PIs), conceded in a recent letter to the Wall Street Journal that the data can be anonymized.

White now claims, as stated in the letter, that they must safeguard the data to protect the patients’ interests; they have a duty of care such that any request for data must be in the context of a defined research proposal deemed acceptable by institutional committee. It is this claim that, were it to succeed, would have a stifling effect on academic research in many fields. If any such claim were recognized, it would not just apply to this trial but be a precedent applied across disciplines to any studies involving human participants.

It must not be allowed to succeed.

It is also false.

First, institutional committees, while no doubt full of people with good intentions, are liable to be over-respectful to their colleagues. They are more likely to support the PIs’ views of what is deemed proper. They would be a potential brake on challenging false reports. Trial investigators would effectively be granted a veto as to who could see their data.

Second, ‘defined research proposals’ need funding and often an infrastructure to support them. Such a requirement would create a closed shop in academic research: the ‘citizen scientist’, the curious student and the lone professor would all be excluded. Often advances come not from planned studies but from discoveries revealed by ‘playing around’ with data. That avenue would be shut off.

Third, this interest, which the PIs claim patients have in data from trials in which they have participated, does not exist. Participants do have certain rights, including a right to know of investigators’ conflicts of interest, something which was not revealed to patients in the PACE trial. They have the right to be treated humanely throughout the trial and to have their health and well-being protected. They have the right to know that their personal details will be secure and any shared data will be properly anonymized, such that no one, for example, could reverse engineer the data and reveal their identity. But once such rights have been safeguarded, then the data are just numbers. There is nothing further to be protected. Investigators cannot invent some duty of care which would give them the right to lock away data in perpetuity, sacred runes that only selected High Priests could see.

Furthermore, if a public interest does exist, then it is in having the data made available as widely as possible. Participants’ time and effort should be properly rewarded by making the greatest use of the data. They should be confident that any analysis of that data, including by the trial investigators, is open to the widest and deepest scrutiny; that, in fact, investigators are not allowed to protect themselves by putting up artificial barriers to inspection of the data. This is an interest shared by the wider society: open science benefits us all. Such an interest is even greater when the data have been obtained by public funding, as with the PACE trial.

Data do not need to be protected. Science, all academic study, is eventually self-correcting. We should have confidence in the robustness of the scientific process, an essential element of which is the greatest possible openness. Paternalistic protection of rows of numbers serves no one other than those with something to hide.

If the PIs are allowed to create this duty of care based on participants’ interest, then every trial investigator will be free to claim it. Drug companies and homeopaths will be able to hide behind this wall, but so will anyone who has conducted a trial using human subjects in medicine, science, psychology, economics, law, philosophy… Every field.

The PACE trial has had a massive impact. It has shaped public policy and perception of the illness in the UK. It has been referenced by health bodies around the world. The findings and the model it purports to evidence have been supported by Professor Sir Simon Wessely, the Lancet and its editor, Richard Horton, NICE, NHS Choices, the Science Media Centre, Sense About Science (UK) and most of the British media, including, for example, Tom Feilden of the BBC.

Patients who challenged the study and rejected the illness model were portrayed as science deniers who were unwilling or unable to accept the truth of their illness, desperate to avoid the stigma of mental illness, erroneously clinging to a false mind/body dualism. They were accused of waging personal vendettas against the PIs and Wessely in particular.

Then about 18 months ago things started to change: separate reports, here and here, to the US NIH and IOM rejected the psychogenic model and pretty much supported everything patients have been saying for decades. Prominent scientists, Lipkin and Hornig from Columbia, Montoya from Stanford and Komaroff from Harvard Universities have been investigating the illness and finding more and more evidence of physiological changes in patients. The NIH has recently announced a multi-million dollar project to study ME as a biological illness. After a small but successful trial of Rituximab, an editorial in New Scientist talked of the scientific story’s being brought full circle, back to the ‘post-viral’ approach of 25 years ago. Alongside Tuller’s blogs and Coyne’s interventions, 40 doctors and scientists wrote an open letter to the Lancet asking for the PACE trial data to be released for analysis. Amongst others, neuroscientist Keith Laws, statistician Andrew Gelman and biologist and campaigner against scientific fraud Leonid Schneider have all posed questions about PACE and its follow-up studies. Professor of mathematical sciences Rebecca Goldin took a detailed look at PACE for the website jointly run by the American Statistical Association and Sense About Science America. Her conclusion was that ‘flaws in this design were enough to doom its results from the start’.

It is estimated that 250,000 patients suffer from ME in the UK. For their sake, the data need to be released and the questions over the trial answered. For everyone’s sake, the PACE PIs cannot be allowed to introduce a restriction on access to data that would act as a massive constraint on a great deal of academic research.

Many thanks for this. All eyes will be on the ICO, although I understand it could still be a long road whatever eventual conclusion they come to apropos this particular appeal. Good to see the concerns about PACE extrapolated to the wider scientific community.

One small detail. You say there have been 150 requests for PACE data. However I think that is for the total amount of information that has been requested, not the number of separate submissions for data. The number of people making submissions for data is something like 35 (can’t find the exact figure right now, somebody else may have it to hand), with each submission asking for several different pieces of data.

Haven’t checked, but there may well be a fair bit of overlap between the submissions, which would significantly reduce that 150.

Of course, there is an easy way for PACE to stop this onerous flood of requests. Hand over the data.

You are right about the number of requests. Thanks to Bobbobme, I have now changed the text to show the true number and linked to evidence which shows there were 35 actual requests for 160 pieces of information

Following this closely as I can, my brain will let me. This really is important for so many people around the world. If the data is held it sets a very worrying precedent for the legitimacy of such trials.

FYI, Retraction Watch is a nonprofit association which publishes information of medical journal publications being retracted for various reasons. They recently interviewed Dr. John Ioannidis of Stanford. Dr. Ioannidis has been sounding the alarm of the hijacking of Evidence Based Medicine to promote false scientific concepts.

To quote from the interview: “John Ioannidis: As I describe in the paper, ‘evidence-based medicine’ has become a very common term that is misused and abused by eminence-based experts and conflicted stakeholders who want to support their views and their products, without caring much about the integrity, transparency, and unbiasedness of science.”

You are welcome. It’s amazing how much time, energy and money has been spent over this matter.

The results of the PACE study are irreproducible without the foundational data being produced to be used in the reproduction of their study.

Irreproducible results are commonly known as “Junk Science”.

Health advisories based on Junk Science are junk-based advisories potentially hazardous to the public.

If I was an an ethical scientists and co-author of this PACE study, I would want my foundational data turned over immediately. I would want to know for certain that my results are reproducible and my advisories to physicians are not harmful to the public.

By fighting so hard from releasing the foundational data, it gives the appearance of these co-authors not wanting their work reviewed to see if it is reproducible. It gives the appearance that they don’t care if they’ve published Junk Science. Nor do they care if their treatment advisories to physicians are potentially harmful to the public.

Whether the perception is correct or not, these authors’ reluctance to have their work reevaluated gives the appearance that they set their hypothesis that ME/CFS are psychological disorders which manifest in physicial symptoms. Then they set out to prove that hypothesis by skewing the data, with public health and safety of no concern to them.

Until they produce the data, their work is irreproducible Junk Science. Health advisories and physician education should not be based upon it until proven otherwise.

One of the more entertaining inconsistencies in what is known about the PACE Trial is that the use of physical measures (the use of an actigraph) was dropped in favour of self-reports of imcrease in activity. It shows a touching faith in the accuracy of reports from patients who, according to the researchers, have an illness entirely based on their ‘false beliefs’.

The theoretical cognitive-behavioural model used to justify CBT & GET posits that the primary pathology is that patients are deluded about their bodily sensations, and that their judgement about them cannot be trusted. (Naturally, only the ‘professional scientific experts’ know the ‘reality’ of the patients’ experience, and have the authority to ‘describe’ it, and recommend the appropriate ‘therapeutic’ responses.)

But magically, by the end of the trial, the patients’ perceptions can be trusted, as measured by the two primary outcome measures, which both happen to be problematic subjective self-reports, that are well known to be heavily influenced by confounding factors, which PACE did not properly control for, and which are persistently and starkly incongruent with objective measures of function.

Where do you start with a critique of something so obviously flawed and unsafe? How do you begin to describe this relentlessly destructive insanity to those who have not experienced it?